In the Microarray & Virology Core, we have brought together a diverse group of NIH-funded investigators from basic science and clinical medicine. These investigators have a common interest in using state-of-the-art technologies to better understand the molecular mechanisms underlying the progression from HCV infection to end-stage liver disease. Our goal is to use DNA microarrays to provide a molecular blueprint of the changes in cellular gene expression that occur at multiple points along the continuum from virus infection to liver disease, including cirrhosis and hepatocellular carcinoma. Our Specific Aims are the following: Aim 1: Supply biological samples for microarray and proteomic analyses and provide molecular biology and virology support. Investigators associated with this core will provide the biological samples used for microarray and proteomic analyses. These samples will come from a variety of in vitro and in vivo systems, including HCV replicon cell lines, cultured primary human hepatocytes, liver biopsy material from patients with recurrent HCV after liver transplantation, and liver biopsy material from patients co-infected with HCV and human immunodeficiency virus (HIV). Aim 2: Use DNA microarrays to profile changes in cellular gene expression that occur during HCV infection and HCV-associated liver disease. This core will leverage the capabilities of a pre-existing microarray facility, the Center for Expression Arrays, to apply the technologies of global gene expression analysis to the study of HCV infection and liver disease. This technology infrastructure will be coupled with expertise in hepatitis C virology, virus-host interactions (including extensive experience in the use of global gene expression profiling), and liver disease and transplantation. Data obtained from these analyses will be provided to the Bioinformatics & Biostatistics core for analysis and integration with data generated by the Proteomics & Modeling core. The information is likely to yield improved diagnostic methods, markers of disease progression, and novel approaches for therapeutic intervention.